Broadly reactive mosaic peptide for influenza vaccine

Abstract

The invention provides for mosaic influenza virus HA and NA sequences and uses thereof.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of the filing date of U.S. application Ser. No. 61 / 785,071, field on Mar. 14, 2013, the disclosure of which is incorporated by reference herein.STATEMENT OF GOVERNMENT RIGHTS[0002]This invention was made with government support under 2008-55620-19132 awarded by the USDA / NIFA. The government has certain rights in the invention.BACKGROUND[0003]Influenza viruses are a significant health concern for animals and humans. The World Health Organization (WHO) estimates that every year influenza virus infects up to 1 billion people, with 3-5 million cases of severe disease and 300,000-500,000 deaths annually (Meltzer et al., 1999). The traditional approach to controlling influenza A virus is based on diagnosis, treatment and prevention through vaccination. Each of these approaches, however, has flaws (e.g., antiviral resistance, incomplete protection, and improper vaccine distribution), e.g., treating every case ...

AI Technical Summary

Benefits of technology

The patent describes a method for creating a universal influenza vaccine that can protect against multiple strains of the virus. The method involves generating a mosaic sequence that includes a combination of natural occurring influenza virus sequences. The mosaic sequence is designed to maximize the coverage of T cell epitopes and provide cross-protection against different strains of the virus. The vaccine is safe, stable, and can be administered to avians and mammals. The method uses a genetic algorithm to optimize the mosaic sequence and can provide immunogenicity against multiple subtypes of the virus. The resulting vaccine has been tested in mice and has shown promising results.

Problems solved by technology

Each of these approaches, however, has flaws (e.g., antiviral resistance, incomplete protection, and improper vaccine distribution), e.g., treating every case with antiviral drugs is not a viable option because it is often ineffective and leads to viral resistance.

However, these approaches have flaws (Iwami et al., 2008; Lipsitch et al., 2007; Lipsitch et al., 2009; Gandon et al., 2001).

Generation of inactivated vaccines (INV) has been optimized for seasonal flu, but presents several challenges for H5N1 viruses, including: 1) continual evolution of the viruses makes predicting a vaccine strain difficult; 2) egg propagation of vaccine stock is hindered due to the high lethality of H5N1 viruses to eggs and the poultry that provide them; and 3) the six to nine month time-period required to produce INV may be too long to protect large populations during a pandemic.

However, they are not recommended in infants, elderly, or immuno-compromised individuals because they can cause pathogenic reactions (Jefferson et al., 2005; Kunisaki and Janoff, 2009; Mostow et al., 1969; Peck, 1968).

Moreover, live vaccines can revert to wild-type viruses, potentially leading to vaccine failure and disease outbreaks (Mostow et al., 1979).

For instance, a critical failure in preparation for influenza pandemics and seasonal epidemics is the absence of a universal vaccine.

Indeed, influenza strains vary by 1-2% per year, and vaccines generally do not elicit protection from one year to the next, necessitating frequent vaccine updates.

This diversity represents a significant challenge to the development of a broadly effective vaccine, as no single viral variant can induce immunity across observed field strains, and incorporating all circulating variants into one multivalent vaccine isn't feasible.

Nevertheless, a broadly effective strategy for H5N1, or other pandemic viruses, control remains elusive.

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